This invention relates to a bioreactor for carrying out cultivation of cells of animals or plants.
Bioreactors for carrying out fermentation or cultivation of cells of animals or plants include a fluid bed type in which a carrier immobilizing cell, enzyme, yeast or microorganism (totally called biological catalyst hereinafter) is maintained in a floating condition and a static bed type in which a carrier stabilizing or immobilizing the biological catalyst fills in a tower or column. The static bed type bioreactor is further classified into a hollow fiber type in which hollow fiber is utilized as a carrier and a packed bed type in which a granular carrier such as foam glass, three-dimensional mesh-shape carrier such as ceramic porous body, honey-comb-shape carrier or multi-layered plate-like carrier is utilized as a carrier.
For example, as a packed bed type bioreactor, there is known a bioreactor in which the granular carrier stabilizing the biological catalyst fills in a cylindrical tank and culture medium is fed into the tank from the lower portion towards the upper portion of the tank. With the bioreactor of this type, the culture medium is likely extruded and the packed bed is composed of a moving phase in which the culture medium flows and a stationary phase (packed material phase) in which the culture medium does not flow at all.
With the bioreactor of the type described above, however, nutritional concentration and dissolved oxygen concentration are gradually reduced during the passing through from an inlet, through which the culture medium with dissolved oxygen is fed, to an outlet, through which a product or used culture medium is recovered, and in the meantime, waste materials reversely increases. For this reason, activity of the biological catalyst is lowered at the outlet of the bioreactor and, hence, the biological catalyst does not effectively fulfill the function and productivity of useful substance is reduced, which constitutes a significant problem.
In order to solve this problem, there has been provided a bioreactor of the type in which the height H of the cylindrical tank is made substantially equal to a distance from the culture medium inlet to a portion just before a portion at which the nutritional concentration and the dissolved oxygen concentration have become their critical values and the productivity of the useful substance have been extremely reduced and the diameter D of the tank is made large to ensure a sufficient inner volume thereof. However, there is a limit for making small the ratio H/D, thus being difficult to scale up the tank.
The biological catalyst likely adheres on the upper surface of the carrier and, hence, the adhesive density of the biological catalyst on the lower side of the carrier is small, which results in the lowering of the productive efficiency. This is also a problem for the bioreactor of the type described above.
In addition, in the conventional bioreactor, since the culture medium is likely extruded and the biological catalyst is poured into the culture medium with relatively high density when the biological catalyst is immobilized in the granular carrier, it is difficult to uniformly immobilize the biological catalyst to the whole carriers in the tank. Accordingly, the immobilization density of the biological catalyst is lowered at a portion near the upper end of the tank (i.e. the outlet side of the bioreactor) and, hence, the productivity of the useful substance for the bioreactor is lowered.
These problems described above have been also caused with a horizontal type bioreactor provided with a tank having an axis extending horizontally, as well as the static bed type bioreactor including the hollow fiber and packed bed type bioreactor.